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Hypertriglyceridemia

Definition
Hypertriglyceridemia is defined as fasting triglycerides ≥ 150 mg/dL, which is associated with an increased risk for coronary heart disease.
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Pathophysiology
Underlying pathophysiology occurs through abnormalities in hepatic VLDL production, and intestinal chylomicron synthesis; dysfunctional LPL-mediated lipolysis or impaired remnant clearance. Primary etiology includes genetic mutations (LPL, APOC3, APOA5 genes), while secondary etiologies may consist of obesity, metabolic syndrome, diabetes, alcohol use, renal disease, pregnancy, and non-alcoholic fatty liver disorder.
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Epidemiology
The prevalence of hypertriglyceridemia in the US is estimated at 29% in men and 21% in women.
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Disease course
Clinical manifestations include eruptive cutaneous xanthomata, lipemia retinalis, tuberous xanthoma, palmar crease xanthomas, hepatosplenomegaly, focal neurologic symptoms (irritability), and recurrent epigastric pain with an increased risk of pancreatitis seen mostly with both familial chylomicronemia and primary mixed hyperlipidemia. Hypertriglyceridemia is associated with an increased risk of coronary heart disease, T2DM mellitus, and acute pancreatitis with a reduction in health-related QoL.
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Prognosis and risk of recurrence
Hypertriglyceridemia with high (150-500 mg/dL) and very high levels (> 500 mg/dL) is associated with increased risk of all-cause mortality with hazard ratio of 1.49 (95% CI 1.36-1.63, p < 0.001) and 3.08 (95% CI 1.46-6.50, p < 0.01), respectively.
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Key sources
The following summarized guidelines for the evaluation and management of hypertriglyceridemia are prepared by our editorial team based on guidelines from the Endocrine Society (ES 2020; 2012), the European Society of Cardiology (ESC/EAS 2020), and the American College of Preventive Medicine (ACPM/ADA/PCNA/ABC/ASPC/AAPA/AGS/AHA/ACC/APhA 2019).
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Guidelines

1.Screening and diagnosis

Indications for screening: screen adults for hypertriglyceridemia with measurement of serum triglycerides as part of a lipid panel at least every 5 years.
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  • Diagnosis

2.Diagnostic investigations

Initial evaluation: evaluate patients with elevation of fasting triglycerides for secondary causes of hypertriglyceridemia, including endocrine conditions and medications. Focus treatment on such secondary causes.
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  • Lipoprotein levels

3.Medical management

General principles: as per ES 2020 guidelines, initiate pharmacologic treatment as adjunct to dietary modifications and exercise to prevent pancreatitis in adult patients with fasting triglyceride levels > 500 mg/dL (5.6 mmol/L).
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  • Fibrates

  • PUFAs

  • Statins

  • Bile acid sequestrants

4.Nonpharmacologic interventions

Lifestyle modification: as per AHA 2019 guidelines, advise implementing a very low-fat diet, avoiding refined carbohydrates and alcohol in adult patients with severe hypertriglyceridemia (fasting triglycerides ≥ 500 mg/dL; ≥ 5.7 mmol/L), especially with fasting triglycerides ≥ 1,000 mg/dL (≥ 11.3 mmol/L), if triglycerides are persistently elevated or increasing after addressing other causes of hypertriglyceridemia.
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5.Specific circumstances

Patients with triglyceride-induced pancreatitis
Avoid performing acute plasmapheresis as first-line therapy to reduce triglyceride levels in patients with triglyceride-induced pancreatitis.
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Avoid administering routine insulin infusion in patients with triglyceride-induced pancreatitis not having diabetes.
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